Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B.

摘要: The expression of the human β-like globin genes follows a well-orchestrated developmental pattern, undergoing two essential switches, first one during weeks gestation (e to γ), and second perinatal period (γ β). γ- β-globin gene switching mechanism includes suppression fetal (γ-globin, HbF) activation adult (β-globin, HbA) transcription. In hereditary persistence hemoglobin (HPFH), γ-globin is impaired leaving these individuals with unusual elevated levels (HbF) in adulthood. Recently, transcription factors KLF1 BCL11A have been established as master regulators switch. Previously, genomic variant gene, identified by linkage analysis performed on twenty-seven members Maltese family, was found be associated HPFH. However, variation HbF among family members, those from other reported families carrying genetic variants KLF1, suggests additional contributors switching. ASF1B downregulated Here, we investigate role erythropoiesis vivo. Mouse-human interspecies protein identity 91.6%. By means knockdown functional assays primary erythroid cultures lineage Asf1b knockout mice, provide evidence that novel contributor steady-state differentiation, while its loss affects balance expression, it has no major